PubMed Health⌕ Search

Biomedical subjects

Takashi Inoue

Publications and source records attributed to Takashi Inoue.

At least 19 recordsLinked to original sources
PubMed2006

Effects of the combination of a dipeptidyl peptidase IV inhibitor and an insulin secretagogue on glucose and insulin levels in mice and rats.

Several combination therapies have been tried for treating of type 2 diabetes to control more effectively fasting hyperglycemia and postprandial hyperglycemia. In this study, we have examined the effects of combining a novel, selective, and competitive dipeptidyl peptidase IV (DPP-IV) inhibitor, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate (E3024), with a representative of one of two types of insulin secretagogues, i.e., either glybenclamide (a sulfonylurea) or nateglinide (a rapid-onset/short-duration insulin secretagogue), on glucose and insulin levels in an oral glucose tolerance test (OGTT) using mice fed a high-fat diet. In addition, we have investigated the effects of these combinations on blood glucose levels in fasting rats. Two-way analysis of variance showed that the combination of E3024 and glybenclamide improved glucose tolerance additively and also caused a synergistic increase in insulin levels in the OGTT in mice fed a high-fat diet. In a similar way, the combination of E3024 and nateglinide ameliorated glucose tolerance additively and raised insulin levels additively. In fasting rats, coadministration of E3024 with glybenclamide or nateglinide treatment did not affect the glucose-lowering effects of the insulin secretagogues. Therefore, a DPP-IV inhibitor in combination with glybenclamide or nateglinide may be a promising option for the treatment of type 2 diabetes, and particularly, for controlling postprandial hyperglycemia in the clinic.

Animals↗
PubMed2006

7-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one is a novel competitive and selective inhibitor of dipeptidyl peptidase IV with an antihyperglycemic activity.

7-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one (ER-319711) is a novel dipeptidyl peptidase (DPP)-IV inhibitor discovered in our laboratories. In this study, we have characterized this DPP-IV inhibitor in vitro and in vivo as an antidiabetic agent. The trifluoroacetate salt form of ER-319711, ER-319711-15, inhibited human DPP-IV with an IC(50) value of 0.089 microM, whereas its IC(50) values toward human DPP8 and DPP9 were >100 microM. Inhibition kinetic pattern analysis indicated that ER-319711-15 inhibited DPP-IV in a competitive manner. ER-319711-15 (1 mg/kg) reduced glucose excursion in an oral glucose tolerance test (OGTT) using Zucker fa/fa rats, with significant increases in plasma insulin and active glucagon-like peptide-1 levels. In an OGTT using mice fed a high-fat diet in which ER-319711-15 (0.1-10 mg/kg) was orally administered at 0 h, and glucose was loaded at 0 and 5 h, this compound improved glucose tolerance dose dependently at both 0- and 5-h glucose loading. Next, we compared efficacy of ER-319711-15, E3024, a competitive DPP-IV inhibitor having an imidazopyridazinone structure, or vildagliptin, a slow-binding and long-acting DPP-IV inhibitor, at the same dose, 10 mg/kg, in the same procedures. At the first glucose challenge, all compounds lowered area under the curve (AUC) values of delta blood glucose between 0 and 2 h significantly to the same degree. At the second glucose load, the AUC values between 5 and 7 h were significantly decreased by ER-319711-15 and vildagliptin, but not by E3024. Therefore, ER-319711 might be a potent, competitive, and selective DPP-IV inhibitor with an antihyperglycemic activity.

Adamantane↗
PubMed2006

E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, is a novel, selective and competitive dipeptidyl peptidase-IV inhibitor.

Dipeptidyl peptidase IV (DPP-IV) inhibitors are expected to become a useful new class of anti-diabetic agent. The aim of the present study is to characterize the in vitro and in vivo profile of E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, which is a novel imidazopyridazinone-derived DPP-IV inhibitor. E3024 inhibited recombinant human and mouse DPP-IV with IC50 values of approximately 100 nM. E3024 inhibited DPP-IV in human, mouse, rat and canine plasma with IC50 values of 140 to 400 nM. In contrast, E3024 did not inhibit DPP-8 or DPP-9 activity. Kinetic analysis indicated that E3024 is a competitive DPP-IV inhibitor. In Zucker fa/fa rats, E3024 (1 mg/kg) reduced glucose excursion after glucose load, with increases in plasma insulin and active glucagon-like peptide-1 levels. In fasted rats, this compound did not cause hypoglycemia. In a rat 4-week toxicological study, no notable changes were found at doses up to 750 mg/kg. The present preclinical studies indicate that E3024 is a novel selective DPP-IV inhibitor with anti-diabetic effects and a good safety profile.

Animals↗
PubMed2006

Diffusion tensor imaging for differentiation of recurrent brain tumor and radiation necrosis after radiotherapy--three case reports.

Fractional anisotropy (FA) is influenced by histological data such as cellularity, vascularity and/or fiber structure in astrocytic tumors. We describe two patients with tumor recurrence and one patient with radiation necrosis who were diagnosed using assessment of FA value. The assessment of FA value in enhanced lesions after radiotherapy may be able to differentiate radiation necrosis from tumor recurrence.

Adult↗
PubMed2006

Comparative analysis of structure, expression and PSD95-binding capacity of Lrfn, a novel family of neuronal transmembrane proteins.

Leucine-rich repeat and fibronectin III domain-containing (Lrfn) has five members in mouse and human (Lrfn1, Lrfn2, Lrfn3, Lrfn4, Lrfn5), and homologues in other vertebrates. Lrfn proteins share leucine-rich repeat (LRR)-immunoglobulin-like (Ig)-fibronectin type III (Fn)-transmembrane domain structure, which is also found in LRR-Ig-Fn superfamily proteins. Mouse Lrfn genes were expressed at adult stage predominantly in the brain. In the course of development, expression of Lrfn1, Lrfn3, and Lrfn4 started from immature neural cells, whereas that of Lrfn2 and Lrfn5 was limited to mature ones. Lrfn1-5 commonly encode glycoproteins spanning the plasma membrane, with their N-terminus located on the extracellular side. C-termini of Lrfn1, Lrfn2 and Lrfn4 were bound by PDZ domains of postsynaptic protein PSD95, re-distributing PSD95 to cell periphery where the Lrfn proteins were detected. These results suggest that Lrfn proteins are neuronal components with a role in the developing or mature vertebrate nervous system.

Amino Acid Sequence↗
PubMed2006

Stationary rescaled pulse in dispersion-decreasing fiber for pedestal-free pulse compression.

By using the concept of a stationary rescaled pulse (SRP), we analyze an adiabatic soliton compression system based on dispersion-decreasing fiber (DDF). We show that a SRP can exist in a DDF with a linearly decreasing dispersion profile and that the SRP resembles a linearly chirped sech2 pulse. According to the analysis, we show numerically that pedestal-free pulse compression is possible by using the SRP.

Journal Article↗
PubMed2006

Impact of collagen subtype proportions in peritoneal tissues on inguinal hernia formation in adults and infants.

Impaired collagen subtype proportions in the matrices results in the alteration of tissue tensile strength, and is an underlying cause of adult inguinal hernia formation; however, it remains unclear if this alteration is also responsible for infantile inguinal hernia formation. We correlated the ratios of collagen type I to type III between adults and infants with and those without an inguinal hernia, in an attempt to clarify the pathogenesis of this disorder. We extracted collagen from the hernial sacs of patients with an inguinal hernia, and from the normal peritoneum of patients without an inguinal hernia. After separation by electrophoresis, the collagen bands were quantified and we compared the ratios of collagen type I to type III between the patients with and those without an inguinal hernia. The ratio of collagen type I to type III was significantly lower in the adults with an inguinal hernia (n=8, 6.17+/-2.69) than in those without an inguinal hernia (n=8, 9.38+/-2.99, P=0.041), whereas the ratios were similar in infants with (n=10, 5.72+/-2.66) and those without an inguinal hernia (n=6, 5.60+/-1.88, P=0.925). Our results showed that tissue weakness was not involved in the pathogenesis of infantile inguinal hernia formation, confirming that simple herniotomy is adequate treatment.

Adult↗
PubMed2006

Association of abdominal obesity with decreased serum levels of carotenoids in a healthy Japanese population.

BACKGROUND & AIMS: Few epidemiological studies have investigated the relationship between abdominal adiposity and serum levels of carotenoids. This study investigated the relationship between total and abdominal obesity and serum levels of carotenoids. METHODS: Study population consisted of healthy Japanese males (n=192) and females (n=398) who attended a health examination screening (age: 49-86 years). Serum carotenoids were measured by high-performance liquid chromatography. Multiple logistic regression analysis was used to provide the multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) of obesity indices for low levels of serum carotenoids. RESULTS: In females, High waist circumference was associated with low levels of serum canthaxanthin (OR=2.00, 95% CI=1.26-3.19) and beta-carotene (BC) (OR=2.01, 95% CI=1.23-3.28). High waist hip ratio was also associated with low levels of serum alpha- carotene and BC (OR=2.44, 95% CI=1.49-4.03, and OR =1.97, 95% CI=1.20-3.28, respectively). Similar results were obtained when body mass index was added to confounding factors. In males, however, there were no significant associations between obesity indices and serum levels of carotenoids. CONCLUSIONS: Our results suggest that abdominal fat accumulation is associated with oxidative stress as determined by low levels of serum carotenoids in females. In males, further study excluding the effect of strong confounding factors, including smoking, is needed.

Abdominal Fat↗
PubMed2006

Adsorption behavior of antimicrobial peptide histatin 5 on PMMA.

Adsorption of antimicrobial peptide histatin 5 on a poly(methyl methacrylate) denture base may serve to prevent biofilm formation, leading to a reduction of denture-induced stomatitis. This study focused on adsorption behavior of histatin 5 onto PMMA surfaces modified using a cold plasma technique and the effectiveness of histatin 5 adsorption for reducing Candida albicans biofilm formation by the quartz crystal microbalance-dissipation (QCM-D) technique. PMMA spin-coated specimens were treated with oxygen (O(2)) plasma using a plasma surface modification apparatus. The amount of histatin 5 adsorbed onto the PMMA treated with O(2) plasma is more than six times greater than that adsorbed onto untreated PMMA. The degree of histatin 5 adsorption had a negative correlation with the contact angle, whereas that of zeta-potential showed no significant correlation. XPS analysis revealed that the introduction of the carboxyl and O(2) functional groups were observable on the O(2) plasma-treated PMMA. Increased surface hydrophilicity and the formation of the carboxyl could be responsible for histatin 5 adsorption on plasma-treated PMMA. There is no significant difference between histatin-adsorbed PMMA and control PMMA for C. albicans initially attached. On the contrary, the amount of C. albicans colonization on histatin-adsorbed PMMA was significantly less than the control.

Adsorption↗
PubMed2006

Control of bisphosphonate release using hydroxyapatite granules.

The efficacy of hydroxyapatite (HAp) as a carrier was investigated to establish a method of local administration of bisphosphonates (Bps), which has currently been administered systemically. HAp granules (300-500 microm in size) with different physicochemical features were prepared by altering the sintering temperature. To ascertain the physicochemical properties of the HAp granules, their crystallinity was assessed using X-ray diffraction, the surface morphology was examined under scanning electron microscopy, and the specific surface area and calcium dissolution were evaluated. Different Bps-HAp composites were subsequently prepared and the concentration of Bps released from these composites was measured. The influence of Bps-HAp composites on the rate of osteoclast survival was also evaluated. The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. These findings indicated that Bps-HAp composites could be locally administered as a drug delivery system to areas with bone resorption.

Animals↗
PubMed2006

Cognitive impairment associated with intraoperative and postoperative hypoperfusion without neurologic deficits in a patient undergoing carotid endarterectomy.

BACKGROUND: Neuropsychological testing detects cognitive impairment in 20% to 30% of patients after carotid endarterectomy (CEA). CASE DESCRIPTION: A 51-year-old man with asymptomatic right cervical internal carotid artery (ICA) stenosis underwent a CEA. Intraoperative transcranial regional cerebral oxygen saturation monitoring revealed ischemia in the right cerebral hemisphere during ICA clamping and transient hyperemia subsequent to ICA declamping. The patient recovered without the appearance of new neurologic deficits. Brain single-photon emission computed tomography performed immediately after CEA showed a decrease in cerebral blood flow in the right cerebral hemisphere. Diffusion-weighted magnetic resonance imaging showed no new abnormal findings. Positron emission tomography performed 2 months after surgery revealed decreased cerebral metabolic rate of oxygen in the right cerebral hemisphere, and neuropsychological testing demonstrated a decline in performance IQ relative to preoperative levels. CONCLUSIONS: Intraoperative ischemia and postischemic delayed hypoperfusion in CEA can impair cognition even in the absence of development of postoperative neurologic deficit.

Brain↗
PubMed2006

Clinical significance of hiatal hernia in the development of gastroesophageal reflux after distal gastrectomy for cancer of the stomach.

BACKGROUND AND AIMS: The relationship between gastroesophageal reflux disease and sliding hernia is controversial, especially following distal partial gastrectomy in patients with gastric cancer. The aim of this study was to examine the relationship between gastroesophageal reflux disease and sliding hernia of the esophagus after distal gastrectomy using the gastroesophageal scintigraphy and endoscopy. METHODS: Forty-five distal gastrectomy patients diagnosed with cancer of the stomach were studied. Twenty-five patients presented with reflux symptoms, such as heartburn and/or regurgitation and 20 patients exhibited no reflux symptoms. All of the patients were examined by gastroesophageal scintigraphy and their reflux indices were determined. Thirty-eight of the patients underwent upper endoscopy and both sliding hernias and reflux symptoms were classified as mild or severe. RESULTS: Sliding hernias were diagnosed in all of the subjects and 65.8% of the patients exhibited reflux symptoms. Evidence of endoscopic esophagitis was noted in only 39.5% of the patients. The reflux indices for the mild and severe hernia groups were 5.03 +/- 2.2 and 10.3 +/- 6.4, respectively (P < 0.05). More severely symptomatic esophagitis was prevalent in the severe hernia group in comparison to the mild group (P < 0.05). CONCLUSION: The results suggest that the onset of gastroesophageal reflux after distal gastrectomy is induced by the surgical procedures and that hiatal hernia may be an important factor in the etiology of reflux esophagitis.

Biopsy↗
PubMed2006

Serum heat shock protein 70 levels and lung cancer risk: a case-control study nested in a large cohort study.

Chronic inflammation contributes to the process of carcinogenesis, but few epidemiologic studies have examined associations with risk of lung cancer. Relationships between lung cancer risk and serum levels of both heat shock protein 70 (Hsp70) and high-sensitivity C-reactive protein (hsCRP) were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 240 deaths from lung cancer were identified through 1999, and 569 controls were matched for sex, age, and study area. Serum levels were measured in 189 cases and 377 controls for Hsp70 and in 209 cases and 425 controls for hsCRP. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, including smoking habits, were 0.83 (0.44-1.58), 1.41 (0.77-2.60), and 1.84 (0.92-3.71) for Hsp70 (P(trend) = 0.042) and 1.13 (0.67-1.91), 0.66 (0.38-1.16), and 1.19 (0.70-2.02) for hsCRP (P(trend) = 0.941). In males, odds ratios (95% confidence intervals) across quartiles were 1.30 (0.59-2.84), 1.74 (0.83-3.67), and 2.49 (1.06-5.85) for Hsp70 (P(trend) = 0.029). High levels of serum Hsp70 might thus be associated with increased risk of lung cancer among Japanese males, although further studies are needed to clarify associations between chronic inflammation and lung cancer.

Adult↗
PubMed2006

Pontine cavernous angioma resected using the subtemporal, anterior transpetrosal approach determined using three-dimensional anisotropy contrast imaging: technical case report.

OBJECTIVE AND IMPORTANCE: We describe a case of brainstem cavernous angioma resected by the subtemporal, anterior transpetrosal approach, selected on the basis of three-dimensional anisotropy contrast (3-DAC) imaging. CLINICAL PRESENTATION: A 64-year-old woman presented with sudden headache and gait disturbance. Anatomic magnetic resonance imaging showed a mass lesion in the left anterolateral part of the pons. On 3-DAC imaging, posteromedial compression of the left corticospinal and corticopontine tracts by the mass lesion was demonstrated. INTERVENTION: The lesion was resected through the anterolateral side of the pons via the subtemporal, anterior transpetrosal approach. Neurological symptoms improved postoperatively, and postoperative 3-DAC imaging demonstrated preservation of the corticospinal and corticopontine tracts. CONCLUSION: The technique of 3-DAC imaging may provide important information regarding neural tracts for the planning of brainstem surgery.

Anisotropy↗
PubMed2006

Bacteriostatic activities of monoacyl sugar alcohols against thermophilic sporeformers.

The bacteriostatic activities of monoacyl sugar alcohols with different acyl chains and hydrophilic heads were examined against some thermophilic sporeformers. Monomyristoyl erythritol and xylitol efficaciously suppressed their spore development. The number and orientation of the hydroxyl groups also played important roles in this activity, and monomyristoyl xylitol exhibited the highest activity among the monomyristoyl sugar alcohols.

Acylation↗
PubMed2006

Stevens-Johnson syndrome associated with intravenous acetazolamide administration for evaluation of cerebrovascular reactivity. Case report.

A 62-year-old man with left middle cerebral artery stenosis manifesting as transient ischemic attack underwent evaluation of regional cerebrovascular reactivity to acetazolamide using single photon emission computed tomography. Three days after intravenous administration of acetazolamide, erythematous eruptions of various sizes appeared on his back and spread over almost his entire body. Subsequently, painful ulcerations developed on his lips, and oral and nasal mucosa, and the conjunctiva became hyperemic, indicating Stevens-Johnson syndrome. The results of the lymphocyte transformation test were positive to only acetazolamide. Stevens-Johnson syndrome, also known as erythema multiforme major, can be life-threatening, and may be induced by intravenous administration of acetazolamide.

Acetazolamide↗